Process of preparing trinuclear cyanine dyes containing a terminal 5-and 6-membered heterocyclic ring system



Patented Dec. 26, 1950 PROCESS OF PREPARING TRIN'UCLEAR CY ANINE DYESCONTAINING A TERMINAL 5- AND 6-MEMIBERED HE'IEROCYCLIC RING SYSTEMThomas R. Thompson, Binghamton, N. Y., assignor to General Aniline &Film Corporation, New York, N. Y., a corporation of Delaware No Drawing.Application December 21. 1948, Serial No. 66,576

4 Claims. (Cl. Milli-240.1)

.ing a cyclammonium base containing a reactive thio group, andcondensing it with a 3-ethylrhodanine to obtain the merocyanineintermediate. This procedure involves two stepsand re- .quires aboutfour hours time. The merocyanine intermediate is then fused with amixture of a cyclammonium base and a quarternizing agent.

such as methyl p-toluenesulfonate for 2 to 3 hours. After cooling themelt, pyridine is added and the mixture reheated under reflux for 20-30minutes. into an aqueous solution of potassium bromide and the final dyeobtained by recrystallization from alcohol. The minimum time requiredfor the latter two steps is approximately from 3 to 4 hours, exclusiveof the time required to cool the reaction mixture.

Theoretically, the trinuclear dyes should be capable of production bytreating a 3-alkylrhodanine with an alkyl salt to efiect quaternizationof the hetero nitrogen atom thereof, and conversion of the thioketogroup to a thioether gr0up, the reaction of the thioether. group withthe reactive grouping of a cyclammonium salt and the linking of theintermediate so formed to a cyanine dye intermediate through theremonium salt to yield thiazolone cyanine dye intermediates.

Because of this, the art has become firmly convinced that in order toprepare trinuclear cyanine dyes of the rhodacarbocyanine type, it isnecessary to treat apreformed merocyanine dye with alkyl salt tosimultaneously eflfect quaternization of the nitrogen atom of therhodanine ring system and the conversion of the thioketo group to athioether group, and to react the 1'6- The reaction mixture is thenpoured 2 sulting salt with a cyclammonium quaternary salt of the typeused in the formation of cyanine dyes. The process steps involved inthis preparation are not only tedious but time consuming.

It is an object of the present invention to provide an improved andsimplified method for the preparation of trinuclear cyanine dyes.

A further object of the present invention is a method of producingtrinuclear cyanine dyes containing a terminal 5- and G-membered.heterocyclic ring system.

A still further object is to provide a. simpler method wherebytrinuclear cyanine dyes in excellent yield are obtained.

Other objects and advantages will become apparent from the followingdescription.

I have found that trinuclear cyanine dyes con taining a terminal 5- andfi-membered heterocyclic ring are prepared in excellent yield and inreadily purifiable form by condensing a 5- or 6-memberedketo-heterocyclic compound containing a reactive acetanilido mono orpolymethine group with a, thiazolone cyanine dye saltwhile heating inthe presence or absence of an alcohol as a solvent-diluent and in thepresence of a tertiary base as a condensing agent on a. steam bath or byheating the reaction mixture at reflux for a period of 5-20 minutes.

The dyes obtained by the foregoing procedure are characterized by thefollowing general formula:

wherein R1 represents the residue of a 5- or 6- membered heterocyclicnucleus,e. g., of a barbituric acid, a thiobarbituric acid, a rhodanine,an oxazoledione, a thiazolone, a pyrazolone, a hydantoin, a,thiohydantoin, and the like, 1!. represents a positive odd integer offrom 1 to 5, R2 represents an alkyl, allyl, aryl, or aralkyl group, e.g., methyl, ethyl, propyl, phenyl, naphthyl, tolyl, benzyl, phenethyland the like, R3 represents an aliphatic, aryl, aralkyl or substitutedgroups of this type, c. g., methyl, ethyl, propyl,

butyl, hydroxyethyl, ethoxyethyl, phenyl, tolyl, naphthyl, benzyl,phenethyl, menaphthyL and 50 ride, "bromide, iodide, or alkyl sulfate,alkyl pthe like, X represents an acid radical, e. g., chlo- (7y,-acetanilidopropenylidene) 3 ethyl toluenesulfonate or perchlorate, and Zrepresents the residue of a heterocyclic nitrogenous nucleus of the typeused in cyanine dyes, e. g., oxazoles, thiazoles, selenazoles, and theirpolycyclic homologues, such as those of the benzene, naphthalene,acenaphthene, and anthracene series, pyridine, and its polycyclichomologues, such as quinoline and aand 'p' naphthaquinolines,perinaphthiazoles, indolenines, diazines, such as pyrimidines andquinazolines, diazoles (e. g., thio-fi-fi-diazole), oxazolines,pyrrolines, thiazolines and selenazolines (the polycyclic compounds ofthese series being substituted if desired in the car:- bocyclic ringswith one or more conventional groups, such as alkyl or aryl, as below,amino, hydroxy, alkoxy, i. e., methoxy, ethoxy, etc, and 'methylenedioxygroups, or by halogenatoms, i." e.,

chlorine, bromine, etc).

The 5- and B-membered heterocyclic intermediates derived from arhodanine', athiazol'onefia 4,- g acetanilidopropenylidene) #3 -"methylf1" plienyl-5"5pyraz'olone '4-'acetanilidomethylene- 3 methyl 1 (2)'pyridyL- 5 pyrazolone 5 'acetanilidomethylene'- 3 allylrhodanine 5acetanilidopropenylidene- 3 allylrhodanine 5 acetanilidomethylene 3phenylrhodanine ,5- ac'etanilidomethylene 3 -e thylrhodanine "5ac'etanilidom'ethylene 3 ethyl 2- thio phenylamino} 4(5) 7 thiazolone51- 51 acetanilidopropenylidene) 3 ethyl 2 thio 2,4(3,5) oXaz oledione 5(5 'acetanilid'o 282,4 pentadienylidene) 5v ('yacetanilidopropenylidene) 2 -thio' 4,6 diketohexahydr'opyrimidine"andthe like. The thiazolone cyanine dye salts utilized as the co'reactantswith the foregoing 5- and 6- membered heterocyclic compounds arecharacterized by the following general formula:

{wherein R R3, X and Z have the same values as above, and are preparedaccordingto the ff method described in my copending application "SerialNo. 786,814, filed November 18, 1947. In

en'eralqthe method 'consistsbf condensing a bstit'uted thioamide with ane-halogen acetic acid. The compounds, in view of theirketomethyleneconfiguration, undergo keto-enol tauftomerism, i. e., the keto group"enolizes'to form a hydroxyl group.

* 'zolylidene) an;

As solvent-diluents employed in the preparation of the dyes of thepresent invention, the following alcohols may be employed: methyl,ethyl, propyl, isopropyl, butyl, benzyl, furfuryl alcohol and the like.Triethylamine, tributylamine and the like are representative of thetertiary bases which I may employ as the catalyst or condensing agent, aL H The 'foll'wng "examples describe the preparation of some of thethiazolone cyanine dye intermediates illustrated by the foregoingformula. Iti's *torbe understood that any one of thethiazolori'efcyaniriedye intermediates as illustrated *in Examples lijto 30 of my copending application Serial-"No. 786,814 may be condensedwith anyone of thej: pr G-membered heterocyclic compounds. containing areactive acetanilido mono or *polymethine group adjacent to a ketogroup.

Example I s H,cs o=o c=cn-o "IA "mixture ofr0.65* g ra-rn *of a(3;5=dimethyl-4- phenylthiazolyliderie) thioaetahilide, 1:0 gram ofbromacetivacidfand2*00. rof acetic '"acid was heated "at- ';=C.-forilE-hour. iTh'e preductgwas precipitatedwith ether and subsequentlywashed with ether-by decantatlon. "Thewiscousproduct -did"'hotsolidifyfind may "be usedflirectly *in d'ye synthesis.

dye salts may be replaced by otheranions, such ass-iodide, thiocyanate,or perchlorate ions, by treating an ,alcohol solution of the dye saltwith an aqueous or aqueous-alcohol solution containing a sodium orpotassium salt of the desired anion.

The following examples describe in detail the improved and simplifiedmethod of preparing trinuclear cyanine dyes from the foregoingthiazolinecyanine dy'esalts, but it is to be understood that they aregiven merely for the purpose of illustration and are not to be construedas limita- A mixture of 3.2 grams of5-acetanilidomethylene-S-allylrhodanine, 4.2. grams of the thiazolinecyanine dye salt of Example I, 50 cc. of methanol and 0.5 cc. oftriethylamine was heated at reflux for 5 minutes. The crude dye wasboiled out with methanol and finally crystallized from pyridine. Theabsorption maximum of this dye in a methanol solution is 610 mp.

/C-H o= o l Example V 0H l' aHs Br A mixture of 3.5 grams of4-acetanilidoallyl- Theianions ofthe foregoing thiazolone cyanine tainarthioketone group in the terminal fiemem- :bered heteroeyclicnitrogenous nucleus, as illustrated in Example IV, may be furthertreated with a quaternizing compound such as methyl iodide. Thequaternized compound is then condensed under reflux conditions with acyclammonium base or salt of the type used in cyanine dyes, such as2-methyl-benzothiazole ethiodide idene-1-phenyl-3-methyl-5-pyrazolone,4.0 grams of the thiazolone cyanine dye salt of Example II, cc. ofmethanol and 1 cc. of triethylamine was heated at reflux for 15 minutes.After cooling, the dye was separated and purified by boiling out withmethanol.

Example VI (EH:CH=CH 2 1-1 After cooling, the dye was separated and aphotographic emulsion is extended to 720 mp,

with a maximum at 680 mp.

While the present invention has been described in considerable detailwith reference to certain preferred procedures and materials employed,it is understood that the improved process of preparing trinuclearcyanine dyes is not limited thereto, and that numerous variations andmodifications described in the foregoing specification may be made as,for example, the dyes which conand the like, having a reactive methylgroup in the a-position to the nitrogenatom thereof, in

the presence of a basic condensing agent such as pyridine. In the firstreaction (alkylation), the trinuclear dye is modified to the extent thatthe nitrogen atom in the 3 position of the oxazoledione hydantoin orrhodanine ring is quaternized and the sulfur atom in the 2 position isconverted to a thioether group. In the second reac tion (condensation),the alkylated trinuclear cyanine dye is condensed with a cyclammoniumbase or salt whereby symmetrical tetranuclear and new unsymmetricaltetranu-clear cyanine dyes are obtained. Accordingly, the scope of myinvention is to be limited solely by the appended claims.

I claim: j

1. A process for the production of trinuclear cyanine dyestuffscomprising heating in the presence of a tertiary basic condensing agenta compound of the formula:

with a. thiazolone cyanine dye salt characterized by the followingformula:

mo-s z o= =on-og wherein n represents a positive integer of from i 1 to3,124 represents the atoms necessary to complete a member selected fromthe class consisting of a 5-membered and G-membered heterocyclic ringsystem, R2 represents a member selected from the class consisting ofalkyl, allyl, aryl, and aralkyl groups, R3 represent a member selectedfrom the class consisting of lower alkyl,

lower hydroxyalkyl, lower alkoxyalkyl, aryl of the benzene andnaphthalene series, and aralkyl groups, X represents an acid radical,and Z re presents the atoms necessary to complete a heterocyclicnitrogenous nucleus of the type used in cyanine dyes.

2. The process for the production of a trinuclear cyanine dyestuffcharacterized by the following formula:

wmeh comprises heating in the presence-of "a dear cyanine dyestufieharacterized byathe 01- "tert'iafry 'basic condensing agent athioazolone lowing-formula:

:tertiary basic, condensing ,agent a 'thiazolone H1C-S cyaninedye-oftheiormula: :4] 4:=CHC/ V Y H0 s- N Y 1 a '1 I CH5 Br with5-acetaniiidomethylene 3-a11y1rhodanine;

T3.'The rprocessifor the production of a trinux'zlear cyanine dyestuficharacterized by'the folw vd p y e 1 y1- lowing formulal-phenyl-2-thiohydantoin; THOMAS R. THOMPSON.

No references cited.

CaHs CeHa 2H5 Br which comprises heating in the presence of a tertiarybasic condensing agent a thiazolone cyanine dye of the formula:

' CaHn 40 Br with 4 aeetanilidopropenylidene '1 -V-.ph'eny1 3-methyl5-vpyrazolone.

4'. The process for the production of .a trinn- Certificate ofCorrection Patent N 0. 2,535,994L December 26, 1950 THOMAS E. THOMPSONIt is hereby certified that error appears in the printed specificationof the above numbered patent requiring correction as follows:

Column 5, lines 36 to 38, Example V, for that portion of the formulareading C-GH C-CH (J-0H read l-OH column 6, line 68, claim 2, for -C=HCread 0H*=C';

and that the said Letters Patent should be read as corrected above, sothat the same may conform to the record of the case in the PatentOffice.

Signed and sealed this 27th day of March, A. D. 1951.

[sEAL] THOMAS F. MURPHY,

Assistant Oomvm'ssz'oner of Patents.

1. A PROCESS FOR THE PRODUCTIONOF TRINUCLEAR CYANINE DYESTUFFSCOMPRISING HEATING IN THE PRESENCE OF A TERTIARY BASIC ONDENSING AGENT ACOMPOUND OF THE FORMULA: